Alzheimer's disease is currently thought to affect as many as 1-3 million people in the USA alone. It has recently been found that the core A4 peptide of the senile plaques (one hallmark of the disease) is derived from a precursor protein 695-750 amino acids long. It is not known how the conversion of the precursor to the A4 protein occurs, but it is possible that specific polypeptide fragments are released into serum or CSF that could be detected by an immunoassay of appropriate specificity and sensitivity. Monoclonal antibodies will be raised to the full length precursor molecule derived from cDNA transfected mammalian cells overexpressing the amyloid precursor. The antibodies will be characterized using our expressed precursor molecule. In addition, antisera will also be prepared from bacterially expressed fragments of the precursor molecule and corresponding synthetic peptides. These antibodies will be used to develop highly sensitive fluorometric immunoassays against various regions of the amyloid precursor. These assays will then be evaluated for their diagnostic potential using numerous patient samples obtained from our comprehensive groups of collaborators.